Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy
Objective: Differentiating forms of autoimmune encephalitis (AE) from other causes of seizures helps expedite immunotherapies in AE patients and informs studies regarding their contrasting pathophysiology. We aimed to investigate whether and how Nuclear Magnetic Resonance (NMR)-based metabolomics co...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/179870 |
| _version_ | 1826125522721046528 |
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| author | Xiong, Wenzheng Yeo, Tianrong May, Jeanne Tan May Demmers, Tor Ceronie, Bryan Ramesh, Archana McGinty, Ronan N. Michael, Sophia Torzillo, Emma Sen, Arjune Anthony, Daniel C. Irani, Sarosh R. Probert, Fay |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Xiong, Wenzheng Yeo, Tianrong May, Jeanne Tan May Demmers, Tor Ceronie, Bryan Ramesh, Archana McGinty, Ronan N. Michael, Sophia Torzillo, Emma Sen, Arjune Anthony, Daniel C. Irani, Sarosh R. Probert, Fay |
| author_sort | Xiong, Wenzheng |
| collection | NTU |
| description | Objective: Differentiating forms of autoimmune encephalitis (AE) from other causes of seizures helps expedite immunotherapies in AE patients and informs studies regarding their contrasting pathophysiology. We aimed to investigate whether and how Nuclear Magnetic Resonance (NMR)-based metabolomics could differentiate AE from drug-resistant epilepsy (DRE), and stratify AE subtypes. Methods: This study recruited 238 patients: 162 with DRE and 76 AE, including 27 with contactin-associated protein-like 2 (CASPR2), 29 with leucine-rich glioma inactivated 1 (LGI1) and 20 with N-methyl-d-aspartate receptor (NMDAR) antibodies. Plasma samples across the groups were analyzed using NMR spectroscopy and compared with multivariate statistical techniques, such as orthogonal partial least squares discriminant analysis (OPLS-DA). Results: The OPLS-DA model successfully distinguished AE from DRE patients with a high predictive accuracy of 87.0 ± 3.1% (87.9 ± 3.4% sensitivity and 86.3 ± 3.6% specificity). Further, pairwise OPLS-DA models were able to stratify the three AE subtypes. Plasma metabolomic signatures of AE included decreased high-density lipoprotein (HDL, −(CH2)n−, –CH3), phosphatidylcholine and albumin (lysyl moiety). AE subtype-specific metabolomic signatures were also observed, with increased lactate in CASPR2, increased lactate, glucose, and decreased unsaturated fatty acids (UFA, –CH2CH=) in LGI1, and increased glycoprotein A (GlycA) in NMDAR-antibody patients. Interpretation: This study presents the first non-antibody-based biomarker for differentiating DRE, AE and AE subtypes. These metabolomics signatures underscore the potential relevance of lipid metabolism and glucose regulation in these neurological disorders, offering a promising adjunct to facilitate the diagnosis and therapeutics. |
| first_indexed | 2024-10-01T06:38:03Z |
| format | Journal Article |
| id | ntu-10356/179870 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:38:03Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1798702024-09-01T15:38:08Z Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy Xiong, Wenzheng Yeo, Tianrong May, Jeanne Tan May Demmers, Tor Ceronie, Bryan Ramesh, Archana McGinty, Ronan N. Michael, Sophia Torzillo, Emma Sen, Arjune Anthony, Daniel C. Irani, Sarosh R. Probert, Fay Lee Kong Chian School of Medicine (LKCMedicine) National Neuroscience Institute Duke-NUS Medical School Medicine, Health and Life Sciences Autoimmune encephalitis Refractory epilepsy Objective: Differentiating forms of autoimmune encephalitis (AE) from other causes of seizures helps expedite immunotherapies in AE patients and informs studies regarding their contrasting pathophysiology. We aimed to investigate whether and how Nuclear Magnetic Resonance (NMR)-based metabolomics could differentiate AE from drug-resistant epilepsy (DRE), and stratify AE subtypes. Methods: This study recruited 238 patients: 162 with DRE and 76 AE, including 27 with contactin-associated protein-like 2 (CASPR2), 29 with leucine-rich glioma inactivated 1 (LGI1) and 20 with N-methyl-d-aspartate receptor (NMDAR) antibodies. Plasma samples across the groups were analyzed using NMR spectroscopy and compared with multivariate statistical techniques, such as orthogonal partial least squares discriminant analysis (OPLS-DA). Results: The OPLS-DA model successfully distinguished AE from DRE patients with a high predictive accuracy of 87.0 ± 3.1% (87.9 ± 3.4% sensitivity and 86.3 ± 3.6% specificity). Further, pairwise OPLS-DA models were able to stratify the three AE subtypes. Plasma metabolomic signatures of AE included decreased high-density lipoprotein (HDL, −(CH2)n−, –CH3), phosphatidylcholine and albumin (lysyl moiety). AE subtype-specific metabolomic signatures were also observed, with increased lactate in CASPR2, increased lactate, glucose, and decreased unsaturated fatty acids (UFA, –CH2CH=) in LGI1, and increased glycoprotein A (GlycA) in NMDAR-antibody patients. Interpretation: This study presents the first non-antibody-based biomarker for differentiating DRE, AE and AE subtypes. These metabolomics signatures underscore the potential relevance of lipid metabolism and glucose regulation in these neurological disorders, offering a promising adjunct to facilitate the diagnosis and therapeutics. Ministry of Health (MOH) National Medical Research Council (NMRC) Published version This study was supported by UCB Pharma. This research was funded in whole or in part by a senior clinical fellow-ship from the Medical Research Council [MR/V007173/1], Wellcome Trust Fellowship [104079/Z/14/Z], BMA Research Grants- Vera Down grant (2013) and Margaret Temple (2017), Epilepsy Research UK (P1201), the Ful-bright UK-US commission (MS-Society research award),the Irish Clinical Academic Training Programme (Well-come Foundation), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre(BRC) and Oxford Health BRC. FP is supported by a Dorothy Hodgkin Early Career Fellowship in Chemistry in association with Somerville College. TY is supported by the Ministry of Health, Singapore through the National Medical Research Council (NMRC/Fellowship/0038/2016 and MOH-TA20nov-002). 2024-08-28T06:00:02Z 2024-08-28T06:00:02Z 2024 Journal Article Xiong, W., Yeo, T., May, J. T. M., Demmers, T., Ceronie, B., Ramesh, A., McGinty, R. N., Michael, S., Torzillo, E., Sen, A., Anthony, D. C., Irani, S. R. & Probert, F. (2024). Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy. Annals of Clinical and Translational Neurology, 11(7), 1897-1908. https://dx.doi.org/10.1002/acn3.52112 2328-9503 https://hdl.handle.net/10356/179870 10.1002/acn3.52112 39012808 2-s2.0-85196647996 7 11 1897 1908 en MRC/Fellowship/0038/2016 MOH-TA20nov-002 Annals of Clinical and Translational Neurology © 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Autoimmune encephalitis Refractory epilepsy Xiong, Wenzheng Yeo, Tianrong May, Jeanne Tan May Demmers, Tor Ceronie, Bryan Ramesh, Archana McGinty, Ronan N. Michael, Sophia Torzillo, Emma Sen, Arjune Anthony, Daniel C. Irani, Sarosh R. Probert, Fay Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy |
| title | Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy |
| title_full | Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy |
| title_fullStr | Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy |
| title_full_unstemmed | Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy |
| title_short | Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug-resistant epilepsy |
| title_sort | distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug resistant epilepsy |
| topic | Medicine, Health and Life Sciences Autoimmune encephalitis Refractory epilepsy |
| url | https://hdl.handle.net/10356/179870 |
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